Colorectal cancer (CRC) is known as the third common cancer worldwide and an important public health problem in different populations. Several genetics and environmental risk factors are involved in the development and progression of CRC including chromosomal abnormalities, epigenetic alterations, and unhealthy lifestyle. Identification of risk factors and biomarkers could lead to a better understanding of molecular pathways involved in CRC pathogenesis. MicroRNAs (miRNAs) are important regulatory molecules which could affect a variety of cellular and molecular targets in CRC. A large number of studies have indicated deregulations of some known tissue-specific miRNAs, for example, miR-21, miR-9, miR-155, miR-17, miR-19, let-7, and miR-24 as well as circulating miRNAs, for example, miR-181b, miR-21, miR-183, let-7g, miR-17, and miR-126, in patients with CRC. In the current review, we focus on the findings of preclinical and clinical studies performed on tissue-specific and circulating miRNAs as diagnostic biomarkers and therapeutic targets for the detection of patients at various stages of CRC.

MicroRNAs: Potential candidates for diagnosis and treatment of colorectal cancer.

Regulation of microRNAs in cancer metastasis

Background
Colorectal carcinoma (CRC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs, miRs) play important roles in carcinogenesis. MiR-32 has been shown to be upregulated in CRC. In this study, we identified the potential effects of miR-32 on some important biological properties of CRC cells, and clarified the regulation of PTEN by miR-32.

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MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells

Early diagnosis of colon cancer (CC) is clinically important, as it can significantly improve patients' survival rate and quality of life. Although the potential role for small extracellular vesicles (sEVs) in early detection of many diseases has been repeatedly mentioned, systematic screening of plasma sEVs derived early CC specific biomarkers has not yet been reported. In this work, plasma sEVs enriched fractions were derived from 15 early-stage (TisN0M0) CC patients and 10 normal controls (NC). RNA sequencing identified a total number of 95 sEVs enriched fraction derived miRNAs with differential expression between CC and NC, most of which (60/95) was in well accordance with tissue results in the Cancer Genome Atlas (TCGA) dataset. Among those miRNAs, we selected let-7b-3p, miR-139-3p, miR-145-3p, and miR-150-3p for further validation in an independent cohort consisting of 134 participants (58 CC and 76 NC). In the validation cohort, the AUC of 4 individual miRNAs ranged from 0.680 to 0.792. A logistic model combining two miRNAs (i.e. let-7b-3p and miR-145-3p) achieved an AUC of 0.901. Adding the 3rd miRNA into this model can further increase the AUC to 0.927. Side by side comparison revealed that sEVs miRNA profile outperformed cell-free plasma miRNA in the diagnosis of early CC. In conclusion, we suggested that circulating sEVs enriched fractions have a distinct miRNA profile in CC patients, and sEVs derived miRNA could be used as a promising biomarker to detect CC at an early stage.

https://www.tandfonline.com/doi/pdf/10.1080/20013078.2019.1643670

Evaluation of circulating small extracellular vesicles derived miRNAs as biomarkers of early colon cancer: a comparison with plasma total miRNAs

Metastasis is a complex, multistep process involved in the progression of cancer from a localized primary tissue to distant sites, often characteristic of the more aggressive forms of this disease. Despite being studied in great detail in recent years, the mechanisms that govern this process remain poorly understood. In this study, we identify a novel role for miR-139-5p in the inhibition of breast cancer progression. We highlight its clinical relevance by reviewing miR-139-5p expression across a wide variety of breast cancer subtypes using in-house generated and online data sets to show that it is most frequently lost in invasive tumors. A biotin pull-down approach was then used to identify the mRNA targets of miR-139-5p in the breast cancer cell line MCF7. Functional enrichment analysis of the pulled-down targets showed significant enrichment of genes in pathways previously implicated in breast cancer metastasis (P < 0.05). Further bioinformatic analysis revealed a predicted disruption to the TGFβ, Wnt, Rho, and MAPK/PI3K signaling cascades, implying a potential role for miR-139-5p in regulating the ability of cells to invade and migrate. To corroborate this finding, using the MDA-MB-231 breast cancer cell line, we show that overexpression of miR-139-5p results in suppression of these cellular phenotypes. Furthermore, we validate the interaction between miR-139-5p and predicted targets involved in these pathways. Collectively, these results suggest a significant functional role for miR-139-5p in breast cancer cell motility and invasion and its potential to be used as a prognostic marker for the aggressive forms of breast cancer.

/pdf/mir-139-5p-is-a-regulator-of-metastatic-pathways-in-breast-1wh4v90jc4.pdf

miR-139-5p is a regulator of metastatic pathways in breast cancer.

MiR-139 inhibits invasion and metastasis of colorectal cancer by targeting the type I insulin-like growth factor receptor.

The invention discloses a recombinant plasmid containing MRP (Multidrug Resistance-associated Protein)-2 genes 3' UTR (Untranslated Region) and reporter genes and application thereof. Constructed MRP-2 gene 3' UTR and reporter gene carriers and pRL-SV40 carriers and microRNA (Ribonucleic Acid) to be screened are co-transfected into a drug-resistance colon cancer cell line; inhibitory activity of microRNA to MRP-2 gene 3' UTR region is responded by simultaneously detecting activities of firefly and renilla luciferase; and thus, a method for targeted screening of reversal tumor multidrug resistance microRNA is established. The method has excellent application prospect in aspects of screening the reversal tumor multidrug resistance microRNA, researching acting mechanism between the reversal tumor multidrug resistance and microRNA and researching the mechanism of the tumor cell multidrug resistance microRNA level.

Recombinant plasmid containing MRP (Multidrug Resistance-associated Protein)-2 genes 3' UTR (Untranslated Region) and reporter genes and application thereof

The invention discloses a recombinant plasmid containing an HSPA1A (heatshockproteinA1A) promoter and a reporter gene as well as a preparation method and an application of the recombinant plasmid. The built HSPA1A promoter sequence reporter gene carrier and pRL-SV40 carrier are co-transfected into a target cell line to subject to photodynamic therapy mediated by photosensitizer, and oxidative stress response degree induced by the photodynamic therapy in the cell is reflected by detecting activities of firefly and renilla luciferase at the same time, so that a new method for screening the photosensitizer can be built. The method has excellent application prospects in the aspects such as screening photosensitive antitumor active matter, researching photodynamic reaction antitumor action mechanism induced by the photosensitizer, and optimizing in vivo and vitro photodynamic therapy condition.

Recombinant plasmid containing HSPA1A (heatshockproteinA1A) promoter and reporter gene as well as preparation method and application of recombinant plasmid

Lin Jiang

Papers

MiR-139 inhibits invasion and metastasis of colorectal cancer by targeting the type I insulin-like growth factor receptor.

Recombinant plasmid containing MRP (Multidrug Resistance-associated Protein)-2 genes 3' UTR (Untranslated Region) and reporter genes and application thereof

Recombinant plasmid containing HSPA1A (heatshockproteinA1A) promoter and reporter gene as well as preparation method and application of recombinant plasmid